New improved antibiotics are continually in demand, for the treatment of human diseases. Antibiotic resistant organisms are continually a problem, particularly in hospitals. Vancomycin has been the last defense. However, especially in hospitals, isolates which are vancomycin resistant are becoming more common. A recent survey found 7.9% of Enterococci in United States hospitals are now vancomycin resistant. “Nosocomial Enterococci Resistant to Vancomycin” Morbidity and Mortality Weekly Report 42(30):597-598(1993). Further resistance of Vancomycin and other antibiotics to Enterococcus faecium is reported, Handwergers. et al., Clin. Infect. Dis. 1993(16), 750-755. Additional resistance to enterococci is reported, Boyle, J F, Clin. Microbiol. 1993(31), 1280-1285. Vancomycin resistance has been reported against Staphylococcus aureus, F. A. Waldvogel, The New England Journal of Medicine, 340(7), 1999. Additional reports include: Murry, B. E. The New England Journal of Medicine, 342(10), 710-721(2000) and Y. Cetinkaya et al, Clinical Microbiology Reviews, 13(4) 686-707(2000). Clearly, antibiotic resistance is a growing public health problem. Having new antibiotics available could provide additional options for physicians in treatment regimens.
The search for new antibiotics which exhibit improved antibacterial activity against vancomycin-resistant isolates and having structures which are not derivatives of vancomycin are particularly appealing targets for screening and synthetic efforts. Structural similarity to existing antibiotics could facilitate the emergence of resistance.
The AC98-antibiotic complex isolated as an unseparated mixture of compounds of undetermined structure produced from cultures of Streptomyces hygroscopicus (strain NRRL 3085) is described in U.S. Pat. No. 3,495,004. It is an object of this invention to provide a novel family of glycopeptide antibiotics which are shown to possess antibacterial activity, especially against vancomycin resistant bacterial isolates and in particular having chemical structures unlike vancomycin.